Human chromosomes express fragile sites and common break sites when cells are grown in special culture media conditions. There is hardly any data for the relative frequency of these sites in normal individuals or in cancer patients. The significance of these sites is unclear. However, since some fragile sites are known to be located at break points of nonrandom chromosomal rearrangements in malignancies, fragile sites may act as factors predisposing to cancer. This study proposes to determine the frequency of fragile sites utilizing peripheral blood from infant monozygotic twins in order that baseline data in normal individuals can be established. Without a normal population for comparison, the significance of fragile sites in cancer patients cannot be accurately assessed. Data will be provided for evaluating the variability in expression of specific sites within individuals and between the twins. Fragile sites and break sites will be studied in affected and nonaffected members of von Hippel-Lindau disease families. Peripheral blood and malignant cells will be compared to establish sites common to both tissues. The frequency and significance of these sites will be compared to the normal twin population in order to determine whether the affected individuals have a higher frequency of certain sites. Two approaches will be used to determine whether fragile sites found in von Hippel-Lindau are located at or near the mutational site causing malignancy. He will use DNA probes located near fragile sites: 1) to compare DNA from tumor tissue with unaffected tissue in individuals with von Hippel-Lindau in order to determine whether certain loci have become chromosomally homozygous, as has been observed for tumor tissue in retinoblastoma and Wilm's tumor, 2) to measure genetic linkage of von Hippel-Lindau to sites near the fragile sites to demonstrate the potential involvement of these loci in von Hippel-Lindau's etiology. Our study is designed to understand the biological significance of these fragile and break sites, and to determine the possible utilization of DNA markers in understanding the nature and origin of tumors.